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Inflammopharmacology Apr 2024Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived... (Review)
Review
BACKGROUND
Prurigo nodularis (PN) is a neuroimmunological skin disease. Severe itching is the most challenging symptom which affects patients' quality of life. T helper 2-derived cytokines, such as interleukin-31 and oncostatin M (OSM), play a crucial role in PN pathogenesis. Nemolizumab and vixarelimab are two biologics acting as IL-31 inhibitors. Vixarelimab also suppresses the OSM activity. This systematic review evaluates the efficacy and safety of nemolizumab and vixarelimab in PN management.
METHODS
A systematic search was conducted in PubMed/Medline, Ovid Embase, and Web of Science up to September 17th, 2023. Clinical trials and cohort studies published in English were included.
RESULTS
Among a total of 96 relevant records, five were included. The results of four studies with 452 patients using nemolizumab showed that a significantly higher percentage of patients treated with nemolizumab demonstrated a reduction in peak pruritus numerical rating scale (PP-NRS) and investigator's global assessment along with improved sleep disturbance (SD) and quality of life than the placebo group. Moreover, one study administered vixarelimab to 49 PN patients, and their finding illustrated a higher rate of subjects who received vixarelimab experienced ≥ 4-point diminution in worst itch NRS, visual analog scale, healing of representative lesions, and SD quality compared to the placebo group.
CONCLUSIONS
IL-31 inhibitors suggest distinct advantages in improving pruritus, sleep quality, and overall quality of life in subjects with moderate-to-severe PN. Further clinical studies are recommended to compare the effectiveness of these biologics to other therapeutic choices.
Topics: Humans; Biological Products; Interleukin Inhibitors; Prurigo; Pruritus; Quality of Life; Interleukins
PubMed: 38332383
DOI: 10.1007/s10787-024-01436-9 -
Cells Dec 2023Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent... (Review)
Review
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant T2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with T1 and T17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.
Topics: Humans; Dermatitis, Atopic; Cytokines; Epidermis; Skin; Lipids
PubMed: 38132113
DOI: 10.3390/cells12242793 -
JAMA Dermatology Mar 2023Patient values and preferences can inform atopic dermatitis (AD) care. Systematic summaries of evidence addressing patient values and preferences have not previously...
IMPORTANCE
Patient values and preferences can inform atopic dermatitis (AD) care. Systematic summaries of evidence addressing patient values and preferences have not previously been available.
OBJECTIVE
To inform American Academy of Allergy, Asthma & Immunology (AAAAI)/American College of Allergy, Asthma and Immunology (ACAAI) Joint Task Force on Practice Parameters AD guideline development, patient and caregiver values and preferences in the management of AD were systematically synthesized.
EVIDENCE REVIEW
Paired reviewers independently screened MEDLINE, Embase, PsycINFO, and CINAHL databases from inception until March 20, 2022, for studies of patients with AD or their caregivers, eliciting values and preferences about treatment, rated risk of bias, and extracted data. Thematic and inductive content analysis to qualitatively synthesize the findings was used. Patients, caregivers, and clinical experts provided triangulation. The GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative Research) informed rating of the quality of evidence.
FINDINGS
A total of 7780 studies were identified, of which 62 proved eligible (n = 19 442; median age across studies [range], 15 years [3-44]; 59% female participants). High certainty evidence showed that patients and caregivers preferred to start with nonmedical treatments and to step up therapy with increasing AD severity. Moderate certainty evidence showed that adverse effects from treatment were a substantial concern. Low certainty evidence showed that patients and caregivers preferred odorless treatments that are not visible and have a minimal effect on daily life. Patients valued treatments capable of relieving itching and burning skin and preferred to apply topical corticosteroids sparingly. Patients valued a strong patient-clinician relationship. Some studies presented varied perspectives and 18 were at high risk for industry sponsorship bias.
CONCLUSIONS AND RELEVANCE
In the first systematic review to address patient values and preferences in management of AD to our knowledge, 6 key themes that may inform optimal clinical care, practice guidelines, and future research have been identified.
Topics: Humans; Female; Adolescent; Male; Dermatitis, Atopic; Caregivers; Pruritus; Asthma; Eczema
PubMed: 36696136
DOI: 10.1001/jamadermatol.2022.6045 -
Allergy and Asthma Proceedings Nov 2017Although the pathophysiology of pruritus has been extensively studied in recent years, with many resultant advancements, management of pruritus is still enigmatic,... (Review)
Review
BACKGROUND
Although the pathophysiology of pruritus has been extensively studied in recent years, with many resultant advancements, management of pruritus is still enigmatic, particularly in chronic cutaneous diseases, such as atopic dermatitis, chronic urticaria, allergic contact dermatitis, cutaneous T-cell lymphoma, and uremic pruritus. The recent finding of the involvement of interleukin (IL) 31 in the pathogenesis of chronic pruritus has provided a novel approach to the management of chronic inflammatory skin disorders. The present report provided an in-depth overview of the role of IL-31 in chronic skin diseases and the possible diagnostic and therapeutic applications in the management of these diseases.
METHODS
A systematic review of IL-31 was conducted by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A review of a total of 45 published research articles revealed that the majority of these articles focused on the role of IL-31 in causation of pruritus and in the worsening of the disease in atopic dermatitis. Other publications examined interleukin in other pruritic diseases (cutaneous T-cell lymphoma, uremic pruritus, allergic contact dermatitis, chronic urticaria). In almost every disease, IL-31 levels were reported to be correlated with the pathology and often with pruritus. The cutaneous injection of IL-31 resulted in a long-lasting itching sensation, and the use of monoclonal antibodies that targeted IL-31 led to a reduction in pruritus.
CONCLUSION
The use of monoclonal antibodies against mediators involved in the pathogenesis of chronic skin diseases has shown promising results. Antibodies that target IL-31, in particular, its receptor A, showed interesting results in atopic dermatitis and decreased pruritus. In subsequent years, the use of these new therapeutic strategies could change the scenario of pruritic skin diseases. However, further studies are needed to more rigorously examine the effects of IL-31 cascade blockage in different chronic skin diseases and to confirm efficacy and the safety of these new therapeutic approaches.
Topics: Antibodies, Monoclonal; Dermatitis, Atopic; Female; Humans; Interleukins; Male; Pruritus; Skin Diseases
PubMed: 29046191
DOI: 10.2500/aap.2017.38.4080 -
Pathology Oncology Research : POR Oct 2014Neuroendocrine tumors of the extrahepatic bile ducts (EBNETs) are very rare. The aim of the present review is to elucidate the characteristics of EBNETs, their treatment... (Review)
Review
Neuroendocrine tumors of the extrahepatic bile ducts (EBNETs) are very rare. The aim of the present review is to elucidate the characteristics of EBNETs, their treatment and prognosis. An exhaustive systematic review of the literature was performed from 1959 up-to-date. One hundred articles, describing 150 cases were collected. Each article was carefully analyzed and a database was created. The most common symptoms were jaundice (60.3 %) and pruritus (19.2 %). Cholelithiasis co-existed in 15 cases (19.2 %). Hormone- and vasoactive peptide- related symptoms were present in only 7 cases (9 %). The most frequent sites were found to be the common hepatic duct and the proximal common bile duct (19.2 %). Surgical management was considered the main treatment for EBNETs, while excision of extrahepatic biliary tree (62.82 %) with portal vein lymphadenectomy (43.6 %) was the most popular procedure. EBNETs are extremely rare. Their rarity makes their characterization particularly difficult. Up to date the final diagnosis is made after surgery by pathology and immunohistochemistry findings. The present analysis of the existing published cases elucidates many aspects of these tumours, giving complete clinicopathological documentation.
Topics: Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Humans; Neuroendocrine Tumors; Prognosis
PubMed: 24917351
DOI: 10.1007/s12253-014-9808-4 -
The Australasian Journal of Dermatology May 2022Hypertrophic scars (HTS) are elevated scars which occur due to abnormalities in wound healing after injury and may be associated with pain, pruritus and functional... (Meta-Analysis)
Meta-Analysis Review
Hypertrophic scars (HTS) are elevated scars which occur due to abnormalities in wound healing after injury and may be associated with pain, pruritus and functional impairment. Despite multiple available treatment options, there is no universal approach to treating HTS. We searched the Web of Science (Core Collection), MEDLINE and EMBASE databases. Title, abstract and full-text screening, along with data extraction, were performed in duplicate. Risk of bias was assessed using the Cochrane risk-of-bias tool. The Vancouver Scar Scale (VSS) scores and mean differences were used for meta-analysis. We screened 3800 abstracts and included 34 randomised controlled trials evaluating treatments for HTS in adults. Silicone and laser modalities improved VSS scores by 5.06 (95% CI: 6.78, 3.34) and 3.56 (95% CI: 5.58, 1.54), respectively. Intralesional triamcinolone combined with silicone or 5-fluorouracil was superior to intralesional triamcinolone monotherapy. Limitations of this study include exclusion of studies which did not utilise VSS, and pooling of studies based on common modalities. Further studies are needed to examine the efficacy of existing and emerging treatment modalities for HTS. Our study supports the treatment of HTS in adults with silicone gel or sheets, injected triamcinolone (preferably combined with 5-fluorouracil or silicone products), pulsed dye laser and fractionated CO laser.
Topics: Adult; Cicatrix, Hypertrophic; Fluorouracil; Humans; Keloid; Silicones; Treatment Outcome; Triamcinolone
PubMed: 35099068
DOI: 10.1111/ajd.13790 -
Frontiers in Immunology 2024Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined...
BACKGROUND
Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent.
METHODS
Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE).
RESULTS
Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]).
CONCLUSION
Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).
Topics: Humans; Dermatitis, Atopic; Janus Kinase Inhibitors; Nasopharyngitis; Pruritus; Acne Vulgaris; Headache; Herpes Zoster; Immunoglobulin A; Purines; Sulfonamides; Pyrazoles; Pyrimidines; Azetidines
PubMed: 38464512
DOI: 10.3389/fimmu.2024.1342810 -
Dermatology (Basel, Switzerland) 2022Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood,... (Review)
Review
BACKGROUND
Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood, and the condition is difficult to treat with no targeted therapies. The aim of this systematic review was to review the evidence of therapies for non-atopic CNPG and conduct a meta-analysis of the results.
SUMMARY
We conducted a systematic review of the literature concerning effect of treatment for non-atopic CNPG. Due to few randomized controlled trials (RCTs) and case series, the literature was unfortunately too sparse to conduct a meta-analysis of the results. Instead, we thoroughly report important data from the three existing RCTs and 6 case studies with more than 15 patients. Evaluated therapies include nemolizumab, aprepitant, topical therapy with hydrocortisone and pimecrolimus, thalidomide, UVA phototherapy, pregabalin, and naltrexone. Included RCTs and case studies all had a heterogeneous methodology making direct comparison almost impossible.
KEY MESSAGES
There is sparse evidence for the currently used therapies for non-atopic CNPG. Several RCTs on new therapies are running or in the pipeline, hopefully providing new, effective, and targeted treatment possibilities for CNPG patients both with and without an atopic predisposition.
Topics: Chronic Disease; Graft vs Host Disease; Humans; Hypersensitivity, Immediate; Prurigo; Pruritus; Skin; Thalidomide; Ultraviolet Therapy
PubMed: 35417906
DOI: 10.1159/000523700 -
Archives of Dermatological Research Jul 2023Chronic inflammatory skin disorders are known to affect sleep quality; however, the relationship between hidradenitis suppurativa (HS) and sleep is not well understood....
Chronic inflammatory skin disorders are known to affect sleep quality; however, the relationship between hidradenitis suppurativa (HS) and sleep is not well understood. We performed a systematic review of HS and sleep disorders and sleep quality in HS patients. We identified seven studies comprising 343,870 subjects. We found that HS patients have a higher likelihood of having a sleep disorder such as obstructive sleep apnea, as well as other non-sleep apnea. Several studies showed that patients reported worse sleep quality due to symptoms of HS such as pruritus and pain. HS patients may be at risk for additional cardiovascular comorbidities and poorer quality of life secondary to these sleep disorders and poor sleep quality. Further high-quality research evaluating these associations is warranted.
Topics: Humans; Hidradenitis Suppurativa; Quality of Life; Skin; Comorbidity; Sleep Wake Disorders
PubMed: 36396891
DOI: 10.1007/s00403-022-02460-x -
Journal of the European Academy of... Mar 2022The plethora of pharmacologic treatments used for periorificial dermatitis (POD) makes clinical decision-making challenging. The objectives of this review were to assess... (Review)
Review
The plethora of pharmacologic treatments used for periorificial dermatitis (POD) makes clinical decision-making challenging. The objectives of this review were to assess the efficacy and safety of pharmacological interventions for POD in children and adults. The search was performed on 2 February 2021 and included seven databases and trial registries, with no date or language restrictions Study selection, data extraction and risk of bias assessments were performed independently and in duplicate by two authors, in accordance with a prespecified protocol. Meta-analyses were performed and reported in accordance with PRISMA guidelines. Where meta-analysis was not possible, a narrative synthesis was performed and reported in accordance with SWiM guidelines. The certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Eleven studies representing 733 participants were included. Oral tetracycline may improve physician-reported severity of POD from day 20 onwards (low certainty evidence). Adverse effects may include abdominal discomfort, facial dryness and pruritus. Pimecrolimus cream may improve physician-reported severity slightly after 4 weeks of treatment (MD -0.49, 95% CI -1.02 to 0.04, n = 164, low certainty evidence). Adverse effects may include erythema, herpes simplex virus infection, burning and pruritus. Azelaic acid gel may result in no change in either physician- or patient-reported severity after 6 weeks of treatment. The evidence is very uncertain about the effect of praziquantel ointment on physician-reported severity and skin-related quality of life after 4 weeks of treatment. The evidence is also very uncertain about the effect of topical clindamycin/benzoyl peroxide on physician-reported severity. The body of evidence to inform treatment of POD currently consists of low and very low certainty evidence for important outcomes. Well-designed trials are needed to further investigate treatment options. Data are required for children and from low-middle income countries to improve external validity. Future trials should also include adequate post-treatment follow-up and standardized outcome measures.
Topics: Adult; Child; Dermatitis, Perioral; Emollients; Humans; Pruritus; Quality of Life
PubMed: 34779023
DOI: 10.1111/jdv.17817